TEFLARO™ (ceftaroline fosamil) powder, for solution

Usual Diluents

Standard Dilution [Amount of drug] [Infusion volume] [Infusion rate]

50 mL infusion bags dilution (see the instructions listed below):
[600 mg ] [50 ml] [1 hour]
[400 mg ] [50 ml] [1 hour]

a) Preparation of 600 mg of Teflaro dose in 50 mL
Withdraw 20 mL of diluent from the infusion bag. Proceed to inject entire content of the Teflaro vial into the bag to provide a total volume of 50 mL. The resultant concentration is approximately 12 mg/mL.

b) Preparation of 400 mg of Teflaro dose in 50 mL
Withdraw 20 mL of diluent from the infusion bag. Proceed to inject entire content of the Teflaro vial into the bag to provide a total volume of 50 mL. The resultant concentration is approximately 8 mg/mL.

Dosage and administration.

Stability / Miscellaneous

Vials: HOW SUPPLIED/STORAGE AND HANDLING
Teflaro (ceftaroline fosamil) for injection is supplied in single-use, clear glass vials containing:
600 mg - individual vial (NDC 0456-0600-01) and carton containing 10 vials (NDC 0456-0600-10)
400 mg - individual vial (NDC 0456-0400-01) and carton containing 10 vials (NDC 0456-0400-10)

Unreconstituted Teflaro vials should be stored at 25°C (77°F); excursions permitted to
15-30°C (59-86°F).

These highlights do not include all the information needed to use Teflaro safely and effectively. See full prescribing information for Teflaro™.

TEFLARO™ (ceftaroline fosamil) injection for intravenous (IV) use. Initial U.S. Approval: 2010

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Teflaro and other antibacterial drugs, Teflaro should be used only to treat infections that are proven or strongly suspected to be caused by bacteria.

INDICATIONS AND USAGE
Teflaro™ is a cephalosporin antibacterial indicated for the treatment of the following infections caused by designated susceptible bacteria:

• Acute bacterial skin and skin structure infections (ABSSSI)
• Community-acquired bacterial pneumonia (CABP)

Acute Bacterial Skin and Skin Structure Infections
Teflaro is indicated for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible isolates of the following Gram-positive and Gram-negative microorganisms: Staphylococcus aureus (including methicillin-susceptible and -resistant isolates), Streptococcus pyogenes, Streptococcus agalactiae, Escherichia coli, Klebsiella pneumoniae, and Klebsiella oxytoca.

Community-Acquired Bacterial Pneumonia
Teflaro is indicated for the treatment of community-acquired bacterial pneumonia (CABP) caused by susceptible isolates of the following Gram-positive and Gram-negative microorganisms: Streptococcus pneumoniae (including cases with concurrent bacteremia), Staphylococcus aureus (methicillin-susceptible isolates only), Haemophilus influenzae, Klebsiella pneumoniae, Klebsiella oxytoca, and Escherichia coli.

Usage
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Teflaro and other antibacterial drugs, Teflaro should be used to treat only ABSSSI or CABP that are proven or strongly suspected to be caused by susceptible bacteria. Appropriate specimens for microbiological examination should be obtained in order to isolate and identify the causative pathogens and to determine their susceptibility to ceftaroline. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

DOSAGE AND ADMINISTRATION Return to article top
600 mg every 12 hours by IV infusion administered over 1 hour in adults ≥ 18 years of age.

Dosage adjustment in patients with renal impairment. Return to article top

Preparation of Solutions
Aseptic technique must be followed in preparing the infusion solution. The contents of Teflaro vial should be constituted with 20 mL Sterile Water for Injection, USP. The preparation of Teflaro solutions is summarized in Table 3.

The constituted solution must be further diluted in range between 50 mL to 250 mL before infusion into patients. Appropriate infusion solutions include: 0.9% Sodium Chloride Injection, USP (normal saline); 5% Dextrose Injection, USP; 2.5% Dextrose Injection, USP, and 0.45% Sodium Chloride Injection, USP; or Lactated Ringer's Injection, USP. The resulting solution should be administered over approximately 1 hour.

Constitution time is less than 2 minutes. Mix gently to constitute and check to see that the contents have dissolved completely. Parenteral drug products should be inspected visually for particulate matter prior to administration.

The color of Teflaro infusion solutions ranges from clear, light to dark yellow depending on the concentration and storage conditions. When stored as recommended, the product potency is not affected.

Studies have shown that the constituted solution in the infusion bag should be used within 6 hours when stored at room temperature or within 24 hours when stored under refrigeration at 2 to 8º C (36 to 46º F).

The compatibility of Teflaro with other drugs has not been established. Teflaro should not be mixed with or physically added to solutions containing other drugs.

50 mL infusion bags dilution (see the instructions listed below):

a) Preparation of 600 mg of Teflaro dose in 50 mL
Withdraw 20 mL of diluent from the infusion bag. Proceed to inject entire content of the Teflaro vial into the bag to provide a total volume of 50 mL. The resultant concentration is approximately 12 mg/mL.

b) Preparation of 400 mg of Teflaro dose in 50 mL
Withdraw 20 mL of diluent from the infusion bag. Proceed to inject entire content of the Teflaro vial into the bag to provide a total volume of 50 mL. The resultant concentration is approximately 8 mg/mL.

DOSAGE FORMS AND STRENGTHS
600 mg or 400 mg of sterile Teflaro powder in single-use 20 mL vials.

CONTRAINDICATIONS
Known serious hypersensitivity to ceftaroline or other members of the cephalosporin class.

WARNINGS AND PRECAUTIONS

• Serious hypersensitivity (anaphylactic) reactions have been reported with beta-lactam antibiotics, including ceftaroline. Exercise caution in patients with known hypersensitivity to beta-lactam antibiotics.
• Clostridium difficile-associated diarrhea (CDAD) has been reported with nearly all systemic antibacterial agents, including Teflaro. Evaluate if diarrhea occurs.
• Direct Coombs' test seroconversion has been reported with Teflaro. If anemia develops during or after therapy, a diagnostic workup for drug-induced hemolytic anemia should be performed and consideration given to discontinuation of Teflaro.

ADVERSE REACTIONS
The most common adverse reactions occurring in >2 % of patients are diarrhea, nausea, and rash.
To report SUSPECTED ADVERSE REACTIONS, contact Forest Pharmaceuticals, Inc., at 1-800-678-1605 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

USE IN SPECIFIC POPULATIONS
Dosage adjustment is required in patients with moderate or severe renal impairment and in ESRD patients, including patients on hemodialysis.

Microbiology

Mode of Action
Ceftaroline is a cephalosporin with in vitro activity against Gram-positive and -negative bacteria. The bactericidal action of ceftaroline is mediated through binding to essential penicillin-binding proteins (PBPs). Ceftaroline is bactericidal against S. aureus due to its affinity for PBP2a and against Streptococcus pneumoniae due to its affinity for PBP2x.

Mechanisms of Resistance
Ceftaroline is not active against Gram-negative bacteria producing extended spectrum beta-lactamases (ESBLs) from the TEM, SHV or CTX-M families, serine carbapenemases (such as KPC), class B metallo-beta-lactamases, or class C (AmpC cephalosporinases).

Cross-Resistance
Although cross-resistance may occur, some isolates resistant to other cephalosporins may be susceptible to ceftaroline.

Interaction with Other Antimicrobials
In vitro studies have not demonstrated any antagonism between ceftaroline or other commonly used antibacterial agents (e.g., vancomycin, linezolid, daptomycin, levofloxacin, azithromycin, amikacin, aztreonam, tigecycline, and meropenem).

Ceftaroline has been shown to be active against most of the following bacteria, both in vitro and in clinical infections [see Indications and Usage].

Skin Infections
Gram-positive bacteria
Staphylococcus aureus (including methicillin-susceptible and -resistant isolates)
Streptococcus pyogenes
Streptococcus agalactiae

Gram-negative bacteria
Escherichia coli
Klebsiella pneumoniae
Klebsiella oxytoca

Community-Acquired Bacterial Pneumonia (CABP)

Gram-positive bacteria
Streptococcus pneumoniae
Staphylococcus aureus (methicillin-susceptible isolates only)

Gram-negative bacteria
Haemophilus influenzae
Klebsiella pneumoniae
Klebsiella oxytoca
Escherichia coli

The following in vitro data are available, but their clinical significance is unknown. Ceftaroline exhibits in vitro MICs of 1 mcg/mL or less against most (≥ 90%) isolates of the following bacteria; however, the safety and effectiveness of Teflaro in treating clinical infections due to these bacteria have not been established in adequate and well-controlled clinical trials.

Gram-positive bacteria
Streptococcus dysgalactiae

Gram-negative bacteria
Citrobacter koseri
Citrobacter freundii
Enterobacter cloacae
Enterobacter aerogenes
Moraxella catarrhalis
Morganella morganii
Proteus mirabilis
Haemophilus parainfluenzae

Susceptibility Test Methods
When available, the clinical microbiology laboratory should provide the results of in vitro susceptibility test results for antimicrobial drugs used in local hospitals and practice areas to the physician as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician in selecting an antibacterial drug product for treatment.

HOW SUPPLIED / STORAGE AND HANDLING
Vials:
Teflaro (ceftaroline fosamil) for injection is supplied in single-use, clear glass vials containing:
600 mg - individual vial (NDC 0456-0600-01) and carton containing 10 vials (NDC 0456-0600-10)
400 mg - individual vial (NDC 0456-0400-01) and carton containing 10 vials (NDC 0456-0400-10)

Unreconstituted Teflaro vials should be stored at 25°C (77°F); excursions permitted to
15-30°C (59-86°F).

Reference(s)

Teflaro is a trademark of Forest Laboratories, Inc.
IF95USCFR03
©2010 Forest Laboratories, Inc. All rights reserved.

Principal Display Panel - 400 mg Vial
Rx only NDC 0456-0400-01

TeflaroTM
400 mg/vial
(ceftaroline fosamil) for injection
FOR INTRAVENOUS INFUSION ONLY.

Reconstitute this vial with 20 mL of Sterile Water to obtain a concentration of 20 mg/mL. Further dilute the entire contents before infusing. See package insert tor instructions on reconstitution, dilution, and dosage.

Single use vial - Discard after use
EF95USCFR400 Rev. 10/2010 ; 4/2014